Analysis of Correlation between Gene Expression and Aberrant Epigenetic Status in Alzheimer's Disease Brain

Abstract

Dysregulation of epigenetic mechanisms has been implicated in the pathogenesis of Alzheimer's disease (AD). It has been shown that epigenetic status in promoter regions can alter levels of gene expressions, but their influence on correlated expressions of genes and its dependency on the disease are unclear. Using publicly available microarray and DNA methylation data, this article infer how correlation in gene expression in non-demented (ND) and AD brain may be influenced by genomic promoter methylation. Pearson correlation coefficients of gene expression levels between each of 123 known hypomethylated genes and all other genes in the microarray dataset were calculated, and the mean absolute coefficients were obtained as an overall strength of gene expression correlation of the hypomethylated gene. The distribution of the mean absolute coefficients showed that the hypomethylated genes can be divided into two, by the mean coefficients above or below 0.15. The division of the hypomethylated genes by the mean coefficients was more evident in AD brain than in ND brain. On the other hand, hypermethylated genes had a single dominant group, and the majority of them had the mean coefficient below 0.15. These results suggest that the lower the DNA methylation, the higher the correlation of gene expression levels with the other genes in microarray data. The strength of gene expression correlation was also calculated between known AD risk genes and all other genes in microarray data. It was found that AD risk genes were more likely to have the mean absolute correlation coefficients above 0.15 in AD brain, when the evidence for their association with AD was strong, suggesting the link between DNA methylation and AD. In conclusion DNA methylation status is intimately associated with correlated gene expression, particularly in AD brain.